Integration and validation of host transcript signatures, including a novel 3-transcript tuberculosis signature, to enable one-step multiclass diagnosis of childhood febrile disease.

Background: Whole blood host transcript signatures show great potential for diagnosis of infectious and inflammatory illness, with most published signatures performing binary classification tasks. Barriers to clinical implementation include validation studies, and development of strategies that enable simultaneous, multiclass diagnosis of febrile illness based on gene expression.

Methods: We validated five distinct diagnostic signatures for paediatric infectious diseases in parallel using a single NanoString nCounter® experiment.

Diagnosis of childhood febrile illness using a multi-class blood RNA molecular signature.

Background: Appropriate treatment and management of children presenting with fever depend on accurate and timely diagnosis, but current diagnostic tests lack sensitivity and specificity and are frequently too slow to inform initial treatment. As an alternative to pathogen detection, host gene expression signatures in blood have shown promise in discriminating several infectious and inflammatory diseases in a dichotomous manner. However, differential diagnosis requires simultaneous consideration of multiple diseases.

Group A streptococcal disease in paediatric inpatients: a European perspective.

Unlabelled: Group A streptococcal (GAS) disease shows increasing incidence worldwide. We characterised children admitted with GAS infection to European hospitals and studied risk factors for severity and disability. This is a prospective, multicentre, cohort study (embedded in EUCLIDS and the Swiss Pediatric Sepsis Study) including 320 children, aged 1 month to 18 years, admitted with GAS infection to 41 hospitals in 6 European countries from 2012 to 2016.

Pulmonary non-tuberculous mycobacteria in colonisation and disease in The Gambia.

The clinical relevance of pulmonary non-tuberculous mycobacteria (PNTM) in The Gambia is unknown. The aim of this study was to estimate the prevalence of non-tuberculous mycobacteria (NTM) in colonisation, and the burden of clinically relevant pulmonary NTM (PNTM) disease in The Gambia. This was a cross-sectional study of the prevalence of NTM in participants aged ≥ 15 years, in a nationwide tuberculosis (TB) prevalence survey between December 2011 and January 2013.

Osteoarticular Infections in Pediatric Hospitals in Europe: A Prospective Cohort Study From the EUCLIDS Consortium.

Background: Pediatric osteoarticular infections (POAIs) are serious diseases requiring early diagnosis and treatment.

Methods: In this prospective multicenter cohort study, children with POAIs were selected from the European Union Childhood Life-threatening Infectious Diseases Study (EUCLIDS) database to analyze their demographic, clinical, and microbiological data.

Results: A cohort of 380 patients with POAIs, 203 with osteomyelitis (OM), 158 with septic arthritis (SA), and 19 with both OM and SA, was analyzed.

Etiology of Kidney Diseases With Proteinuria in the Gambia/West Africa.

Unlabelled: In West Africa, kidney diseases are frequently seen, but diagnostic and therapeutic options are poor due to limited access to specialized facilities. To unravel the etiology and develop clinical guidelines, we collected clinical data and results of kidney biopsies in 121 pediatric and mostly young adult patients with edema and proteinuria in The Gambia. Workup included clinical examination, urine and serum analysis, and kidney biopsy findings.

Detectable A Disintegrin and Metalloproteinase With Thrombospondin Motifs-1 in Serum Is Associated With Adverse Outcome in Pediatric Sepsis.

Importance: A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 is hypothesized to play a role in the pathogenesis of invasive infection, but studies in sepsis are lacking.

Objectives: To study A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 protein level in pediatric sepsis and to study the association with outcome.

Design: Data from two prospective cohort studies.

Rheumatic heart disease in The Gambia: clinical and valvular aspects at presentation and evolution under penicillin prophylaxis.

Background: Rheumatic heart disease (RHD) remains the leading cause of cardiac-related deaths and disability in children and young adults worldwide. In The Gambia, the RHD burden is thought to be high although no data are available and no control programme is yet implemented. We conducted a pilot study to generate baseline data on the clinical and valvular characteristics of RHD patients at first presentation, adherence to penicillin prophylaxis and the evolution of lesions over time.

Defeating Paediatric Tuberculous Meningitis: Applying the WHO "Defeating Meningitis by 2030: Global Roadmap".

Children affected by tuberculous meningitis (TBM), as well as their families, have needs that lie at the intersections between the tuberculosis and meningitis clinical, research, and policy spheres. There is therefore a substantial risk that these needs are not fully met by either programme. In this narrative review article, we use the World Health Organization (WHO) "Defeating Meningitis by 2030: global roadmap" as a starting point to consider key goals and activities to specifically defeat TBM in children.

Neurocognitive and functional impairment in adult and paediatric tuberculous meningitis.

In those who survive tuberculous meningitis (TBM), the long-term outcome is uncertain; individuals may suffer neurocognitive, functional and psychiatric impairment, which may significantly affect their ability to lead their lives as they did prior to their diagnosis of TBM. In children who survive, severe illness has occurred at a crucial timepoint in their development, which can lead to behavioural and cognitive delay. The extent and nature of this impairment is poorly understood, particularly in adults.

Mortality and morbidity in community-acquired sepsis in European pediatric intensive care units: a prospective cohort study from the European Childhood Life-threatening Infectious Disease Study (EUCLIDS).

Background: Sepsis is one of the main reasons for non-elective admission to pediatric intensive care units (PICUs), but little is known about determinants influencing outcome. We characterized children admitted with community-acquired sepsis to European PICUs and studied risk factors for mortality and disability.

Methods: Data were collected within the collaborative Seventh Framework Programme (FP7)-funded EUCLIDS study, which is a prospective multicenter cohort study aiming to evaluate genetic determinants of susceptibility and/or severity in sepsis.

Predictive value of C-reactive protein for tuberculosis, bloodstream infection or death among HIV-infected individuals with chronic, non-specific symptoms and negative sputum smear microscopy.

Background: C-reactive protein (CRP) is an inflammatory biomarker that may identify patients at risk of infections or death. Mortality among HIV-infected persons commencing antiretroviral therapy (ART) is often attributed to tuberculosis (TB) or bloodstream infections (BSI).

Methods: In two district hospitals in southern Malawi, we recruited HIV-infected adults with one or more unexplained symptoms present for at least one month (weight loss, fever or diarrhoea) and negative expectorated sputum microscopy for TB.

Childhood tuberculosis is associated with decreased abundance of T cell gene transcripts and impaired T cell function.

The WHO estimates around a million children contract tuberculosis (TB) annually with over 80 000 deaths from dissemination of infection outside of the lungs. The insidious onset and association with skin test anergy suggests failure of the immune system to both recognise and respond to infection. To understand the immune mechanisms, we studied genome-wide whole blood RNA expression in children with TB meningitis (TBM).

Caesarean section wound infections and antibiotic use: a retrospective case-series in a tertiary referral hospital in The Gambia.

Ours is the first published study to examine post-Caesarean section (CS) wound infections in The Gambia. We explored risk factors and clinical management retrospectively at a large referral hospital over a 12-month period. A total of 777 cases were identified and records for 682 (88%) were retrieved.

TST positivity in household contacts of tuberculosis patients: a case-contact study in Malawi.

Background: Screening household contacts of active tuberculosis (TB) patients is recommended for TB control. Due to resource constraints this rarely occurs in lower income countries. Demographic and clinical features of index cases may influence the likelihood of onwards TB transmission.

Invasive bacterial infections in Gambians with sickle cell anemia in an era of widespread pneumococcal and hemophilus influenzae type b vaccination.

There is relatively little data on the etiology of bacterial infections in patients with sickle cell anemia (SCA) in West Africa, and no data from countries that have implemented conjugate vaccines against both Streptococcus pneumoniae and Haemophilus influenzae type b (Hib).We conducted a retrospective analysis of SCA patients admitted to the Medical Research Council Unit, The Gambia, during a 5-year period when there was high coverage of Hib and Pneumococcal conjugate vaccination. We evaluated 161 admissions of 126 patients between April 2010 and April 2015.

Respiratory Virus-Associated Severe Acute Respiratory Illness and Viral Clustering in Malawian Children in a Setting With a High Prevalence of HIV Infection, Malaria, and Malnutrition.

Background:  We used data from 4 years of pediatric severe acute respiratory illness (SARI) sentinel surveillance in Blantyre, Malawi, to identify factors associated with clinical severity and coviral clustering.

Methods:  From January 2011 to December 2014, 2363 children aged 3 months to 14 years presenting to the hospital with SARI were enrolled. Nasopharyngeal aspirates were tested for influenza virus and other respiratory viruses.

The History, Role, and Value of Public Directors on Certifying Boards: The American Board of Ophthalmology Experience.

The mission of the American Board of Ophthalmology (ABO) is to serve the public by improving the quality of ophthalmic practice through a continuing certification process that fosters excellence and encourages continual learning. Since 2001, achieving this mission has been enhanced by including public directors in the ABO governance. We review the evolution of including nonprofessional members on the governing boards of professional regulatory and self-regulatory organizations generally, provide history about the incorporation of non-professional public directors into the governance structure of the American Board of Medical Specialties and the ABO, and offer insights about the perceived impact of public directors on the ABO.

Endoscopic capacity in West Africa.

Background: Levels of endoscopic demand and capacity in West Africa are unclear.

Objectives: This paper aims to: 1. describe the current labor and endoscopic capacity, 2.

Acute rheumatic fever and rheumatic heart disease in resource-limited settings.

Poststreptococcal complications, such as acute rheumatic fever (ARF) and rheumatic heart disease (RHD), are common in resource-limited settings, with RHD recognised as the most common cause of paediatric heart disease worldwide. Managing these conditions in resource-limited settings can be challenging. We review the investigation and treatment options for ARF and RHD and, most importantly, prevention methods in an African setting.

Rabies post-exposure prophylaxis at a clinic in Fajara, The Gambia.

Background: The Gambia is a popular holiday destination that is classified as a high-risk area for rabies exposure by the WHO.

Methods: This was a retrospective study of 49 subjects with rabies exposure attending The Medical Research Council Clinical Service, The Gambia, for treatment. Their demographics, details of exposure and treatment delivery were evaluated.